A5008322025- RNA modifications and cancer
- PI3K/AKT/mTOR signaling in cancer
- Pancreatic and Hepatic Oncology Research
- Advanced biosensing and bioanalysis techniques
- Nitrogen and Sulfur Effects on Brassica
- Cancer-related molecular mechanisms research
- Genomics, phytochemicals, and oxidative stress
- RNA Interference and Gene Delivery
- Tannin, Tannase and Anticancer Activities
- Cancer Genomics and Diagnostics
- Ubiquitin and proteasome pathways
- Cancer Mechanisms and Therapy
- RNA and protein synthesis mechanisms
- Cancer Cells and Metastasis
- Protein Degradation and Inhibitors
- Histone Deacetylase Inhibitors Research
- Synthesis and biological activity
- Invertebrate Immune Response Mechanisms
- Colorectal Cancer Screening and Detection
- Lung Cancer Research Studies
- Proteoglycans and glycosaminoglycans research
- Advanced Nanomaterials in Catalysis
- Redox biology and oxidative stress
- Polyamine Metabolism and Applications
- Microbial metabolism and enzyme function
Garvan Institute of Medical Research
2019-2023
The Kinghorn Cancer Centre
2019-2023
UNSW Sydney
2007-2022
Prince of Wales Hospital
2021
Northern Sydney Local Health District
2018
The University of Sydney
2018
Children's Cancer Institute Australia
2007-2017
Abstract Heterogeneous subtypes of cancer-associated fibroblasts (CAFs) coexist within pancreatic cancer tissues and can both promote restrain disease progression. Here, we interrogate how cells harboring distinct alterations in p53 manipulate CAFs. We reveal the existence a p53-driven hierarchy, where with gain-of-function (GOF) mutant educate dominant population CAFs that establish pro-metastatic environment for GOF null alike. also demonstrate educated by may be reprogrammed either or...
Abstract The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance this crosslinking and stabilizing fibrillar collagens its known role tumor desmoplasia. Using small-molecule drug-design approaches, we generated validated PXS-5505, first-in-class highly selective potent pan-lysyl inhibitor. We demonstrate vitro vivo that inhibition decreases chemotherapy-induced pancreatic desmoplasia stiffness, reduces cancer cell invasion metastasis,...
Histone deacetylase (HDAC) inhibitors reactivate tumor suppressor gene transcription; induce cancer cell differentiation, growth arrest, and programmed death; are among the most promising new classes of anticancer drugs. Myc oncoproteins can block differentiation promote proliferation malignant transformation, in some cases by modulating target transcription. Here, we show that tissue transglutaminase (TG2) was commonly reactivated HDAC neuroblastoma breast cells but not normal contributed...
Cancer is one of the most common causes death worldwide. Two types cancer that have high mortality rates are pancreatic and lung cancer. Despite improvements in treatment strategies, resistance to chemotherapy presence metastases common. Therefore, novel therapies which target silence genes involved regulating these processes required. Short-interfering RNA (siRNA) holds great promise as a therapeutic disease-causing genes. However, siRNA requires delivery vehicle enter cell allow it its...
βIII-tubulin (encoded by TUBB3) expression is associated with therapeutic resistance and aggressive disease in non-small cell lung cancer (NSCLC), but the basis for its pathogenic influence not understood. Functional differential proteomics revealed that regulates of proteins malignant growth metastases. In particular, adhesion-associated tumor suppressor maspin was differentially regulated βIII-tubulin. Functionally, suppression altered morphology, reduced spheroid outgrowth, increased...
Non-small cell lung cancer (NSCLC) remains the most common cause of death worldwide due its resistance to chemotherapy and aggressive tumor growth. Polo-like kinase 1 (PLK1) is a serine-threonine protein which overexpressed in cells, plays major role regulating A number PLK1 inhibitors are clinical trial; however, poor bioavailability off-target effects limit their efficacy. Short-interfering-RNA (siRNA) holds promise as class therapeutics, can selectively silence disease-causing genes....
Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups PanNETs, termed T1, T2 T3, distinct patterns methylation. The T1 subgroup was enriched for functional ATRX, DAXX MEN1 wild-type genotypes. contained mutations in recurrent chromosomal losses half genome no association between regions loss levels. were larger had lower MGMT gene body, which showed positive...
The cyclin-dependent kinase inhibitor, p21 WAF1 , induces cell-cycle arrest and can act as a tumor suppressor. However, increasing evidence indicates that also increase resistance to some anticancer therapies thus promote growth. mechanisms explaining this paradox have not been explained. We found conditioned media from MCF-7 breast cancer cells transfected with -specific small interfering RNA (siRNA) significantly reduced endothelial cell migration, invasion vascular sprouting. Liquid...
Abstract Background Histone deacetylase inhibitors (HDACIs) have many effects on cancer cells, such as growth inhibition, induction of cell death, differentiation, and anti-angiogenesis, all with a wide therapeutic index. However, clinical trials demonstrate that HDACIs are more likely to be effective when used in combination other anticancer agents. Moreover, the molecular basis for anti-cancer action is still unknown. In this study, we compared different combinations agents anti-angiogenic...
Poly(ethylene glycol) (PEG) conjugates of Dicer-substrate small interfering RNA (DsiRNA) have been prepared to investigate a new siRNA release strategy. 3′-sense or 5′-antisense thiol-modified, blunt-ended DsiRNAs, inhibiting enhanced green fluorescent protein (eGFP) expression, were covalently conjugated PEG with varying molecular weights (2, 10, and 20 kg/mol) through stable thioether bond using Michael addition reaction. The DsiRNA 2 kg/mol (both strand conjugated) the 10 efficiently...
The Wnt receptors ROR1 and ROR2 are generating increased interest as cancer therapeutic targets but remain understudied in pancreatic ductal adenocarcinoma (PDAC). Compared to canonical Wnt/ β-catenin signalling, the role of noncanonical signalling PDAC remains largely unknown. Only one study has investigated prognostic significance receptor, PDAC. No studies have PDAC.Here, we performed analysis mRNA expression three publicly available datasets ICGC-PACA-AU (n = 81), TCGA-PAAD 150)...
Abstract Facilitating informed decision‐making regarding genetic testing is a core component of counseling practice. Internationally, shifting toward gene panels and genomic testing, including whole exome genome sequencing to improve diagnostic yield cost‐effectiveness. This study explored genetics practitioners’ current experience with tests the associated evolution Genetics practitioners experience, were purposively invited participate in semi‐structured telephone interview snowball...
The Australian Pancreatic Cancer Screening Program (APCSP) offers endoscopic ultrasound surveillance for individuals at increased risk of pancreatic ductal adenocarcinoma (PDAC) with all participants requiring assessment by a Familial Service before or after study enrolment. Individuals aged 40-80 years (or 10 younger than the earliest PDAC diagnosis) were eligible APCSP entry if they had 1) ≥ two blood relatives (at least one first-degree association); 2) clinical genetic diagnosis...
Pancreatic cancer (PC) is an aggressive disease with a dismal 5-year survival rate. Surveillance of high-risk individuals hoped to improve outcomes by detection precursor lesions or early-stage malignancy.Since 2011, national cohort recruited through St Vincent's Hospital, Sydney, has undergone prospective PC screening incorporating annual endoscopic ultrasound, formal genetic counselling and mutation analysis as appropriate. PancPRO, Bayesian risk assessment model, was used estimate...
Abstract Non‐Small Cell Lung Carcinoma (NSCLC) remains a leading cause of cancer death. Resistance to therapy is significant problem, highlighting the need find new ways sensitising tumour cells therapeutic agents. βIII‐tubulin associated with aggressive tumours and chemotherapy resistance in range cancers including NSCLC. expression has been shown impact kinase signalling NSCLC cells. Here, we sought exploit this interaction by identifying co‐activity between suppression small‐molecule...
Abstract BACKGROUND: Non-small cell lung cancer (NSCLC) has a dismal prognosis and remains the most common cause of death worldwide. Expression βIII-tubulin, encoded by TUBB3 gene, is associated with clinical resistance aggressive disease in NSCLC1. Herein, we interrogated mechanistic role βIII-tubulin regulating tumorigenic potential NSCLC. METHODS: Functional studies involved independent clones NSCLC H460 cells stably expressing shRNA targeting controls (non-functional) rescue established...
<p>Supplementary Table 1: Proteins that were identified to be differentially expressed in the cytoplasmic fraction of H460 βIII-tubulin shRNA expressing NSCLC cells. Supplementary 2: nuclear cells.</p>
<p>A) A graph showing a decrease in βIII-tubulin mRNA expression A549 NSCLC cells stably expressing shRNA (pRS/βIIISH61) vs. control (pRS/CtrlSH27). B) Representative western blot demonstrating potent knockdown of protein GAPDH was used loading control, n = 3 experiments.</p>
<p>Two-Dimensional Difference Gel Electrophoresis (2D-DIGE) of cytoplasmic and nuclear extracts H460 NSCLC cells expressing βIII-tubulin or control shRNA.</p>
<p>Purity of nuclear and cytoplasmic fractions isolated from βIII-tubulin shRNA control NSCLC cells.</p>
<p>Validation of proteins found to be differentially expressed in H460 βIII-tubulin shRNA expressing cells.</p>
<p>βIII-tubulin shRNA NSCLC cells show increased maspin expression.</p>
<p>2D-DIGE experimental design.</p>